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Apatinib has been demonstrated to be effective and safe among patients with gastric cancer failing after at least two lines chemotherapy. This study aimed to evaluate its effectiveness and safety of low‐dose apatinib for the treatment of gastric cancer in real‐world practice. We performed a prospective, multicenter observation study in a real‐world setting. Patients with advanced gastric cancer more than 18 years old were eligible and received low‐dose apatinib (500 mg or 250mg per day) therapy. The median progression‐free survival (PFS), median overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety were assessed. Between September 2017 and April 2019, a total of 747 patients were enrolled. The mPFS was 5.56 months (95% CI 4.47‐6.28), and mOS was 7.5 months (95% CI 6.74‐8.88). Four patients achieved complete response, 47 achieved partial response, and 374 patients achieved stable disease. The ORR was 6.83% and DCR was 56.89%. In addition, multivariate Cox regression analysis indicated that hand‐foot syndrome was one independent predictor for PFS and OS. The most common adverse events (AEs) at any grade were hypertension (36.55%), proteinuria (10.26%), hand‐foot syndrome (33.53%), fatigue (24.9%), anemia (57.35%), leukopenia (44.49%), thrombocytopenia (34.21%), and neutropenia (53.33%). Grade 3‐4 AEs with incidences of 5% or greater were anemia (13.97%), thrombocytopenia (7.14%), and neutropenia (6.67%). No treatment‐related death was observed during the treatment of apatinib. The prospective study suggested that low‐dose apatinib was an effective regimen for the treatment of advanced gastric cancer with tolerable or controlled toxicity in real world. Trial registration: NCT03333967. [ABSTRACT FROM AUTHOR]